Family Planning, Fertility, and Rheumatoid Arthritis

Sexual activity limited by physical disability is one of several reasons that researchers posit is the cause of infertility in women with rheumatoid arthritis.

As treatment options continue to evolve and rheumatoid arthritis (RA) becomes less disabling, more women with the disease may choose to pursue pregnancy. However, meeting the family planning needs of these patients requires frank discussion and careful coordination.

For as many as 42% of female patients with RA diagnosed with the disease before family completion, the time to pregnancy exceeds 12 months, as compared with only 10% to 17% of the general population.1 Because antirheumatic treatment has to be adjusted for most women with RA before they start trying to conceive, a longer time to pregnancy can mean prolonged periods with less adequate RA control and an increased risk for permanent joint damage.1 Understanding the underlying mechanisms of subfertility in patients with RA and treating those mechanisms whenever possible is an important step forward in the care of patients with RA who are planning to grow their families.

“Women
with RA who wish to become pregnant may be reassured that many women with RA
have successful pregnancies, particularly when their diseases are well
controlled at the time of conception,” says Nicole Hunt of the Division of
Rheumatology and Clinical Immunology, Department of Medicine, University of
Pittsburgh.2

Reasons for
Reduced Family Size With RA

Research
has shown that for more than 60 years women with RA have had smaller families and
higher rates of nulliparity than women without the disease.2 In a
Dutch study of 245 women with RA, 42% reported a delay of more than 12 months
to conception.3

Reasons
that women with RA have trouble growing their families include2,3:

higher rates of
miscarriage;

physical disability that limits sexual activity;

maternal age;

menstrual irregularity;

disease activity;

reduced levels of anti-Mullerian hormone, which is an indicator for ovarian reserve in women;

daily dose of prednisolone higher than 7.5 mg.

use of non-steroidal anti-inflammatory drugs (NSAIDs);

ovulatory dysfunction; and

endometriosis.

High
disease activity may contribute to a smaller family size and a higher incidence
of infertility in patients with RA, as severe illness has been found to reduce
sexual function due to pain and immobility.3 Another theory is that
women with an RA diagnosis may have concerns about their abilities to care for
children due to their level of fatigue and physical limitations. Fears about
whether medications might affect a developing fetus or if the disease may be
passed on to their children may also play a role.2 For many women
with RA, however, the reasons for infertility are unexplained.2

“The
high percentage of RA patients diagnosed by the gynecologist with unexplained
subfertility may imply that fertility in female RA patients is influenced by
disease-related factors,” said Jenny Brouwer, MD, Erasmus MC, University
Medical Center Rotterdam, Rotterdam, The Netherlands.

A
Dutch study found a significant association of periconceptional NSAID use with
unexplained subfertility.1 Researchers found that NSAIDs may interrupt
the ovulatory process, possibly leading to luteinized unruptured follicle (LUF)
syndrome.1 In LUF syndrome, although ovulation is inhibited, menstrual
cycle length and regularity is unaffected, meaning patients with LUF would
probably be classified as ovulatory during examination.1

Men, RA, and Infertility

Although
RA is 3 times more common among women, men still develop the disease.2

RA
has not been definitively linked to infertility in men, but some RA medications
prescribed to men have been linked to subfertility.2 Men with RA who
experience infertility may require semen analysis testing for further diagnosis.2

Regarding
men with RA, NSAIDs, hydroxychloroquine, and TNF-α inhibitors don’t seem to
increase the risk for adverse outcomes in paternally exposed children, although
data on NSAID and hydroxychloroquine exposure are scant.2 Sulfasalazine
has been associated with lack of sperm and decreased sperm motility, but these
effects may be reversible.2 Earlier research suggested that
methotrexate be discontinued by fathers before attempting to conceive, but recent
studies conclude that methotrexate-exposed fathers do not have higher rates of major
birth defects, growth restriction, or preterm birth.2

Prescriber Beware

Health
care providers may need to adjust treatment plans for women with RA who are
planning to conceive. As previously stated, NSAIDs should be prescribed with caution.
By preventing the rupture of the luteinized follicle, NSAIDs may impair
ovulation and lengthen time to pregnancy.3 NSAIDs also have been
linked to an increased risk for miscarriage, although these data have been
somewhat unclear.2 Women with RA should discontinue taking methotrexate
at least 3 months prior to becoming pregnant because it is an abortifacient and
may cause birth defects.2 Other drugs that could contribute to the
subfertility in patients with RA include potentially teratogenic
disease-modifying antirheumatic drugs (DMARDs).3

“The
use of various DMARDs reduces the disease activity, but the reproductive health
of women, who are the ones predominantly affected by RA, should also be taken
into consideration when formulating a treatment plan,” said Richard Oluyinka
Akintayo, Department of Rheumatology, Lagos State University Teaching Hospital,
Ikeja, Nigeria.3

Assisted
Reproductive Technology and Family Planning

The
number of women with RA during the fertile years is increasing.4 In
the Dutch study, the percentage of participants who were subfertile and received
fertility treatments was almost 50% higher than in the general population.1

Assisted
reproductive technology (ART) has helped women all over the world to conceive, however
a Danish study conducted over 23.5 years found that this infertility treatment
was less successful for women with RA. Specifically, the study found that ART
treatments in women with RA provided a significantly decreased chance of live
birth per embryo transfer compared with ART treatments in women without RA.4
Researchers believe this is due to challenges with embryo implantation.4
However, the study also found that women with RA who had a corticosteroid
prescribed before embryo transfer may have an improved chance of a live birth
compared with women with RA who did not take a corticosteroid before embryo
transfer, although the findings were not definitive.4

Applying the
Research to Your Practice

Although
research suggests that some women with RA may experience subfertility, it’s recommended
that health care providers avoid assuming that women with RA are infertile,
subfertile, or uninterested in pursuing pregnancy.

Women
with rheumatic diseases should receive risk counseling from their health care
providers if they are considering pregnancy.2 Specifically, the
patient’s RA should be well controlled on safe, anti-rheumatic drugs for at
least 3 to 6 months before she gets pregnant to provide the best chance for a
successful outcome.2 And though it may seem counterintuitive, contraception
may offer unique benefits to women with RA. For example, contraception can help
delay a desired pregnancy until an optimal time when the patient is using
pregnancy-compatible medications and her disease is well controlled, thereby bolstering
maternal, fetal, and pregnancy outcomes.2

Researchers
recommend that health care providers initiate a conversation about family
planning with all patients of reproductive age at the time they are diagnosed
with RA and before starting or changing medications with fetotoxic potential.

“In
daily practice, when an RA patient wishes to conceive, NSAIDs should be
avoided, and early consultation with an expert rheumatologist and a fertility
specialist should be considered to optimize the patient’s chance of a complete
family,” said Brouwer.1